Synthesis of oligosaccharides by using solid-phase method and hybrid method of solid-phase and liquid-phase

研究了固相法和固液相混合法高效合成低聚糖的方法。我们以前建立了“化学钓鱼”方法，利用固载膦与叠氮化物的特定反应，从反应混合物中选择性地筛选出所需的具有叠氮功能的化合物。将该方法应用于固相合成诱导子五糖。并对糖蛋白N-连接低聚糖的合成进行了研究。我们提出了一种利用(Bu_3SN)_2自由基反应裂解三氯乙氧羰基的新方法，并将该方法应用于固相合成，利用其邻基参与效应，实现了在固体载体上利用TROC基团进行立体控制的β-氨基糖基化反应。以4，6-O-亚苄基甘露醇N-苯基三氟乙酰亚氨酸酯为糖基供体，TMSOTf为酸催化剂(β=1：9)，实现了立体选择性α:β-甘露糖化反应。我们还建立了以N-邻苯二甲酰唾液酸苯基三氟乙酰亚胺为供体，TMSOTf为酸催化剂的α选择性唾液酸化反应。我们先前报道了基于亲和分离的合成，通过利用标签与识别标签的分子之间的特定亲和力，将具有标签部分的目标化合物从反应混合物中快速分离出来。在本研究中，我们利用豆荚和乙醚标签与固载铵离子的相互作用，发展了新的SAS方法。将该方法应用于包括Lewis X在内的小分子寡糖库的快速合成，合成了多种免疫刺激糖偶联物、脂多糖和肽聚糖的部分结构和类似物，以阐明它们的生物学功能。

Efficient synthesis of oligosaccharides by using solid-phase method and hybrid method of solid-phase and liquid-phase was investigated. We previously established "Chemical Fishing" method, where desired compound having azide function is selectively fished out of the reaction mixture by using the specific reaction between solid-supported phosphine and azide. This method was applied to the solid-phase synthesis of the elicitor pentasaccharide. Synthetic study of N-linked oligosaccharide of glycoprotein was also investigated. We developed a novel method for cleavage of trichloroethoxycarbonyl(Troc) group by radical reaction using (Bu_3Sn)_2. This method was then applied to solid-phase synthesis and rendered the use of Troc group for stereocontrolled β-glucosaminilation on solid-support by using its neighboring group participation effect. Stereoselective β-mannosylation was effected by using 4,6-O-benzylidene mannnosyl N-phenyltrifluoroacetimidate as a glycosyl donor and TMSOTf as an acid catalyst(α:β=1:9). We also established α-selective sialylation by using N-phthaloyl sialic acid phenyltrifluoroacetimidate as a donor and TMSOTf as an acid catalyst.We previously reported Synthesis based on affinity separation(SAS), where desired compound having a tag moiety is rapidly separated from a reaction mixture by using specific affinity between the tag and the molecule that recognizes the tag. In the present study, we developed the new SAS method using the interaction between podand ether tag and solid-supported ammonium ion. The present method was applied to the rapid synthesis of small oligosaccharide library including Lewis X. Various partial structures and analogues of immunostimulating glycoconjugate lipopolysaccharide and peptidoglycan were synthesized in order to elucidate their biological functions.